The present invention relates to an odorless formulation for treating mucosal discontinuities. The present invention also includes a method for making the formulation and a method for using the formulation.
The term, “mucosal discontinuities” as used herein refers to discontinuities which are present or which are inflicted on mucosal tissue of living beings. Mucosal discontinuities include wounds which are internal or external bodily injuries or lesions which are caused by a physical force or by another mechanism. The physical force is one or more of a mechanical, chemical, viral, bacterial, or thermally induced physical force. The physical force disrupts the normal continuities of biologic structures of living beings.
Mucosal discontinuities include contusions, wounds in which the skin is unbroken, incisions, wounds in which the skin is broken by a cutting instrument, lacerations, and wounds in which the skin is broken by a dull or blunt instrument. Discontinuities include wounds caused by accident or by surgical procedures.
Patients who suffer major wounds and other discontinuities benefit from treatment that enhances healing and pain relief. Wound healing mechanisms comprise a series of processes whereby tissue, such as mucosal tissue, is repaired. In particular, in repair, specialized tissue is regenerated. New tissue is reorganized.
Wound healing typically comprises three phases. A first phase is an inflammation phase that lasts up to about 3 days. A second phase is a cellular proliferation phase that lasts from about 3 to 12 days. A third phase is a remodeling phase that lasts from about 3 days to 6 months.
During the first inflammation phase, platelet aggregation and clotting form a matrix which traps plasma proteins and blood cells to induce the influx of various type of cells. During the second cellular proliferation phase, new connective or granulation tissue and blood vessels are formed. During the third remodeling phase, granulation tissue is replaced by a network of collagen and elastin fibers leading to the formation of scar tissue.
When cells are injured or killed as a result of a wound, the wound healing step is desirable to resuscitate the injured cells and to produce new cells to replace the dead cells. The healing process produces a reversal of cytotoxicity, a suppression of inflammation, and a stimulation of cellular viability and proliferation. Wounds typically require low levels of oxygen in the initial stages of healing to suppress oxidative damage and higher levels of oxygen in the later stages of healing to promote collagen formation by fibroblasts.
One type of mucosal discontinuity includes aphthous ulcers. Aphthous ulcers are believed to be caused by a virus, in some instances, as well as genetics, trauma, hormonal changes, and gastrointestinal factors.
Aphthous ulcers have shapes that range from single, multiple, round, to oval shaped. The ulcers range in size from 2–40 mm. The ulcers occur on mucus membranes of the tongue, cheeks, lips, soft and hard pallets, gingiva, pharynx and on the floor of the mouth. The ulcers are also found in the genital, anal, and in conjunctival mucosae.
Aphthous ulcers are extremely painful lesions. The ulcers appear as small macular red lesions. The ulcerated area quickly undergoes necrosis, leaving a sharply defined rounded ulcer, varying from about 2 to 5 mm in diameter. The ulceration is fairly deep with a yellow white base representing the tissue at the surface. The margin of the ulcer somewhat indurated and the margin of the mucosae has a surrounding erythematous zone. The marginal erythema ranges from slight to extensive, depending upon the degree of the secondary bacterial involvement.
The aphthous ulcer is present for about seven days and it undergoes gradual healing. It heals as a general rule in approximately 10–14 days and does not tend to leave a scar. Characteristically, there is a recurrent pattern of one of more of these ulcers. The ulcers recur as soon as one month apart and there are cases where, for a period of years, the individual is never without ulcers. New ulcers form as the existing lesions heal. In other cases, aphthous ulcer attacks may occur two to three times during a year. The lesions also often appear following some intense emotional stress, but they may first appear following a gradual change in environment or following an emotional situation in a non-familiar environment.
Aphthous ulcers have been found to occur in greater frequency in women. The ulcers appear several days prior to the menstrual period. The first encounter with aphthous stomatitis for women frequently follows the onset of menstruation. Women susceptible to these lesions often report freedom from the lesions during pregnancy. There is a tendency for a greater frequency of these lesions in females than in males. Although they occur at any age level, the ulcers occur more often in adults.
The term “Periadenitis Mucosa Necrotica Recurrens” is sometimes used to describe aphthae that coalesce to form an elongated, deep ulcerated area. From a symptomatic standpoint, it has found that about 24–48 hrs. before onset of an aphthous lesion, there is a vague discomfort, sometimes described as a tingling sensation in the area. As the tissue undergoes necrosis and an ulcer forms, the lesions become very painful. The aphthous lesions are often considered the most painful oral ulcerations. The discomfort may become particularly intense during periods of fatigue.
The histopathology of the disease is one where the microscopy picture is non-specific, generally showing an ulceration of the mucosae. The surface epithelium exhibits a central area of destruction. The connective tissue is densely infiltrated with lymphocytes, polymorphonuclear leukocytes, plasma cells, and histocytes. There is evidence of active fibrosis at the base and sides of the ulcerated area.
Differential diagnosis of aphthous ulcers includes traumatic ulcers, acute herpetic stomatitis, stomatitis medicamentosa, and erythema multiforme. The diagnosis of aphthous stomatitis is based upon the clinical manifestation and the patient's history. Biopsies are usually unnecessary due the extreme discomfort involved and are avoided unless necessary to rule out other lesions considered differentially diagnostic.
Many substances in agents have been used in an attempt to cure and or relieve the discomfort of aphthous lesion. For example, cauterizing drugs, such as phenol, chromic acid, alum and silver nitrate, have been used for many years. These agents alleviate pain by destruction of small nerve endings. The healing time of the lesion is prolonged due to the escharotic action of these drugs on the surface epithelium and the active fibrosis at the base and sides of the ulcerated areas. Vitamins have also been tried with inconsistent results. Antibiotics have been used with conflicting results.
One observer found that Aureomycin applied locally, three times a day appeared to have a definite effect. With treatment, the duration of the ulcers was reduced from about 10–5 days and there was an analgesic effect lasting one half to two hours. Temporary relief has also been sought and sometimes achieved by using milk of magnesia or heavy syrups. Other more exotic remedies have been tried with little or no success. These remedies include vaccination with cowpox virus, and nutrient supplements.
U.S. Pat. Nos. 3,920,835, 3,984,556, and 3,988,470, all issued to Van Scott et al., disclose methods for treating acne, dandruff and palmar keratosis, respectively. The methods generally comprise applying to an affected area a topical composition that comprises about 1% to 20% of a lower aliphatic compound composition that contains from 2 to 6 carbon atoms selected from a group consisting of alpha hydroxy acid, alpha-ketoacids and esters thereof, and 3-hydroxybutyric acid in a pharmaceutically acceptable carrier.
U.S. Pat. No. 4,416,982 issued to Tauda et al. discloses a method for decomposing hydrogen peroxide by reacting the hydrogen peroxide with a phenol or aniline derivative in the presence of peroxidase.
One prior art formulation is manufactured by Northern Research Laboratories of St. Paul, Minn. The formulation is a reddish-brown material that has a strong phenolic odor.